X-Ray and Chemical Studies of Metalloporphyrins

该提案的主要重点是发展与结构特性相关的基础知识， 金属卟啉的物理性质，特别是铁衍生物的物理性质，特别是作为 这些涉及对基于血蛋白的生物过程的理解。该方法利用了 分子结构的测定，通常通过X射线衍射，以及相关的详细结构 特征与其他测量属性，并提供足够数量的示例，以确保 结论.在以前的工作中强调的物理性质包括不寻常的电子 结构、磁性（包括自旋态和自旋-自旋耦合）和光谱性质 包括电子顺磁共振（EPR）和穆斯堡尔谱，提供了基本的 这些信息对低分子量物质和血红素蛋白都有用。我们现在 将这种方法扩展到核共振振动光谱学（NRVS），一种同步加速器 一种基于辐射的方法，用于测量位于中心的铁化合物的振动光谱 许多生物分子。NRVS比拉曼或红外光谱具有更高的选择性和更广泛的应用前景 光谱学，允许通过其他方法不可见的模式的检测。大多数化合物 所研究的是具有广泛生物学功能的血红素蛋白衍生物 包括氧的利用、储存和运输、基于气体的信号传导、电子传递、药物 代谢和其他酶促过程。我们正在使用和开发NRVS，以了解 血红素复合物的振动模式的详细性质。这些振动测量可以 提供独特的信息，因为定向单晶测量可以参考详细的 分子结构特征在我们最初的工作中，我们强调了面外的识别 铁-配体振动，这是至关重要的理解的性质铁-咪唑键， 血红素和小的气态配体与铁中心的缔合/解离。铁卟啉盐 研究的化合物包括一些六配位衍生物[Fe（por）（XO）（Im）]（XO = O_2，CO，NO）， 为了检查Fe-Im振动的变化，因为相反的配位体发生了变化，这对 理解血红蛋白氧结合协同性和基于气体的信号传导的问题。功能障碍 这种信号传导导致许多疾病状态，如神经退行性疾病、中风、高血压和 胃肠道疾病，勃起功能障碍和心脏病。我们现在建议延长我们的 实验定向单晶测量在一个新的，复杂的方式。本实验 将检查作为分子特征的函数的面内振动光谱的各向异性; 理论预测和实验偏差表明，新的信息，涉及到 可以获得对键合特征和计算的理解。温度依赖性NRVS 将对选定的系统进行测量，以进一步探索这些系统的动力学问题。 分子包括一氧化氮和分子氧系统。将研究压力的影响 通过在高达约8 GPa的压力下测量NRVS谱。只要有可能， 这些测量将在定向晶体样品上进行。

The main focus of this proposal is to develop basic knowledge that relates the structural properties of metalloporphyrins to their physical properties, especially those of iron derivatives, and particularly as these pertain to an understanding of hemoprotein-based biological processes. The approach utilizes the determination of molecular structure, typically by X-ray diffraction, and relating detailed structural features to other measured properties, with a sufficient number of examples to ensure generality of the conclusions. Physical properties that were emphasized in previous work included unusual electronic structures, magnetic properties including spin state and spin-spin coupling and spectral properties including electron paramagnetic resonance (EPR) and M¿ssbauer spectroscopy that provided fundamental information that are useful for both low-molecular weight species and hemoproteins. We are now extending this approach to Nuclear Resonance Vibrational Spectroscopy (NRVS), a synchrotron radiation-based method used to measure the vibrational spectrum of iron compounds that are at the center of many biomolecules. NRVS is both more selective and more comprehensive than Raman or IR spectroscopy, allowing for the detection of modes not visible by other methods. Most compounds to be studied are related to hemoprotein derivatives that carry out a wide range of biological functions including oxygen utilization, storage and transport, gas-based signaling, electron transport, drug metabolism, and other enzymatic processes. We are using and developing NRVS to understand the detailed nature of the vibrational modes of heme complexes. These vibrational measurements can provide unique information because oriented single crystal measurements can be referenced to detailed molecular structure features. In our initial work, we emphasized the identification of the out-of-plane iron--ligand vibrations that are vital to an understanding of both the nature of the Fe-imidazole bond in hemes and the association/dissociation of small gaseous ligands to the iron center. Iron porphyrinates to be studied include a number of six-coordinate derivatives, [Fe(por)(XO)(Im)] (XO = O2, CO, NO), in order to examine changes in the Fe--Im vibrations as the opposite ligand is changed, important for understanding issues in hemoglobin oxygen-binding cooperativity and gas-based signaling. Dysfunction of such signaling contributes to many disease states from neurodegeneration, stroke, hypertension, and gastrointestinal diseases to erectile dysfunction and heart disease. We now propose to extend our experiments to oriented single-crystal measurements in a novel, complex fashion. In this experiment, we will examine the anisotropy of the in-plane vibrational spectrum as a function of molecular features; both theoretical predictions and experiment deviations suggest that novel information that pertains to understanding bonding features and calculations can be obtained. Temperature-dependent NRVS measurements will be made on selected systems to further explore the dynamical issues of these molecules including both nitric oxide and dioxygen systems. The effect of pressure will be investigated through the measurement of the NRVS spectrum at pressures up to about 8 GPa. Whenever possible, these measurements will be made on an oriented crystal specimen.